The synergistic combination of current biotechnological and nanotechnological research has turned to multienzyme co-immobilization as a promising concept to design biocatalysis engineering. It has also intensified the development and deployment of multipurpose biocatalysts, for instance, multienzyme co-immobilized constructs, via biocatalysis/protein engineering to scale-up and fulfil the ever-increasing industrial demands. Considering the characteristic features of both the loaded multienzymes and nanostructure carriers, i.e., selectivity, specificity, stability, resistivity, induce activity, reaction efficacy, multi-usability, high catalytic turnover, optimal yield, ease in recovery, and cost-effectiveness, multienzyme-based green biocatalysts have become a powerful norm in biocatalysis/protein engineering sectors. In this context, the current state-of-the-art in enzyme engineering with a synergistic combination of nanotechnology, at large, and nanomaterials, in particular, are significantly contributing and providing robust tools to engineer and/or tailor enzymes to fulfil the growing catalytic and contemporary industrial needs. Considering the above critics and unique structural, physicochemical, and functional attributes, herein, we spotlight important aspects spanning across prospective nano-carriers for multienzyme co-immobilization. Further, this work comprehensively discuss the current advances in deploying multienzyme-based cascade reactions in numerous sectors, including environmental remediation and protection, drug delivery systems (DDS), biofuel cells development and energy production, bio-electroanalytical devices (biosensors), therapeutical, nutraceutical, cosmeceutical, and pharmaceutical oriented applications. In conclusion, the continuous developments in nano-assembling the multienzyme loaded co-immobilized nanostructure carriers would be a unique way that could act as a core of modern biotechnological research. Display omitted •Immobilized multienzymatic systems represent a versatile platform for biocatalysis.•Prospective nano-carriers as host for immobilized multienzymatic systems are reviewed.•Biotechnological applications of immobilized multienzymatic systems are outlined.•Improvement of stability and reusability of the co-immobilized enzymes is emphasized.•Future trends for widespread applications of multienzymatic systems are highlighted.